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Basic Science and Pathogenesis

Subodh Kumar1

  • 1Texas Tech University Health and Sciences Center El Paso, El Paso, TX, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
PubMed
Abstract

Insights

Synaptic microRNA-502-3p plays a key role in Alzheimer's disease (AD) by affecting cognitive and synaptic functions. Modulating this microRNA offers a potential therapeutic strategy for AD synaptic dysfunction.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Synapse dysfunction is an early indicator of Alzheimer's disease (AD), preceding neurodegeneration.
  • The role of synapse-specific microRNAs (miRNAs) in AD-related synaptic dysfunction remains largely unexplored.

Purpose of the Study:

  • To investigate the role of synapse-specific miRNAs in Alzheimer's disease (AD).
  • To determine the specific impact of miRNA-502-3p on synaptic function, cognitive performance, and neurotransmission in AD models.

Main Methods:

  • Identified synapse-specific miRNAs from postmortem brain samples of AD patients and controls.
  • Utilized APP/Tau transgenic and wild-type mice to study the effects of miRNA-502-3p.
  • Administered lentivirus for miRNA-502-3p overexpression and suppression in the mouse hippocampus via stereotaxic surgery.

Main Results:

  • Overexpression of miRNA-502-3p impaired cognitive function, reduced synaptic proteins, induced mitochondrial dysfunction, and decreased GABA/glutamate neurotransmission.
  • Suppression of miRNA-502-3p improved cognitive function, increased synaptic proteins, enhanced mitochondrial activity, and restored GABA/glutamate neurotransmission.

Conclusions:

  • Synaptic miRNA-502-3p significantly modulates synaptic function in the context of Alzheimer's disease.
  • Targeting miRNA-502-3p presents a potential therapeutic avenue for restoring synaptic function in AD.

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